Synthesis of C_2- symmetric α, α'-disubstituted azacycloalkanes as chiral building blocks and their application

近年来，C2对称手性化合物被认为是手性助剂和手性构筑块。因此，人们在合成它们方面付出了相当大的努力。众所周知，非手性对称和双官能化底物的双重不对称反应提供了具有对映体增强作用的C2对称手性化合物。通过1，6-庚二烯的双不对称烯丙基硼化、氨基环化和氨基甲基化反应，我们探索了一种新型的C2对称的2，6-二烯丙基哌啶作为手性构筑基块。它的合成用途已被证明在方便地合成与哌啶相关的生物碱，如2，6-反式二烷基哌啶类化合物，如松树和云杉的成分(-)-表二氢哌啶，以及火蚁毒液的成分(2R，6R)-反式茄红菌素A，瓢虫防御性生物碱前球虫碱，以及新的三环生物碱(-)孔雀碱，基于独特的去对称化反应，使用碘代氨基甲基化作为关键步骤，并得到一个烯丙基的保护。将这一程序进一步应用于其他生物碱，如(-)-赖氨酸，目前正在研究中。

Recently, C_2 symmetric chiral compounds have been recognized as chiral auxiliary and chiral building block. Therefore, considerable effort has been directed toward synthesizing them. It is known double asymmetric reaction of achiral symmetric and bifunctionalized substrate provided C_2 symmetric chiral compounds accompanied with enantiomeric enhancements. We explored a novel C_2 symmetric 2, 6-diallylpiperidine as a chiral building block via the double asymmetric allylboration of 1, 6-heptadiene followed by aminocyclization and carbamation. Its synthetic utility has been demonstrated in the expedient synthesis of piperidine-related alkaloids such as of 2, 6-trans-dialkylpiperidines such as (-)-epi-dihydropinidine, a constituent of pine and spruce species, and (2R, 6R)-trans-solenopsin A, a constituent of fire-ant venom, precoccinelline, a ladybug defense alkaloid, and (-) porantheridine, a novel tricyclic alkaloid of Poranthera corymbosa, based on distinctive desymmetrization using iodocarbamation as a key step, along with the protection of one allyl group. Further application of this procedure to other alkaloids such as (-)-lythrandine is currently under investigation.